GENECARD-Gene Identification in Early-Onset CAD

GENECARD-早发 CAD 中的基因识别

• 批准号: 7245060
• 负责人: Elizabeth R Hauser
• 金额: $ 72.28万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7245060
• 关键词: 3q13; Affect; Age; Age of Onset; Age-Years; Arts; Base Pairing; Behavioral; Bioinformatics; Biological; Candidate Disease Gene; Cause of Death; Chromosomes; Chromosomes, Human, Pair 3; Clinical; Collection; Complex; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Coupled; DNA; Data Set; Disease; Environment; Environmental Risk Factor; Family; Follow-Up Studies; Genes; Genetic; Genetic Heterogeneity; Genome; Genomics; Genotype; Goals; High Pressure Liquid Chromatography; Human Genetics; Individual; Life Style; Lod Score; Maps; Microsatellite Repeats; Motivation; Myocardial Infarction; Nuclear Family; Numbers; Operative Surgical Procedures; Other Genetics; Physiological; Predisposition; Prevention strategy; Principal Investigator; Procedures; Public Health; Research Personnel; Resources; Risk; Sampling; Score; Siblings; Single Nucleotide Polymorphism; Site; Susceptibility Gene; Testing; Tissue-Specific Gene Expression; Woman; Work; base; clinical phenotype; density; disability; early onset; follow-up; gene environment interaction; gene interaction; genetic linkage analysis; genome-wide linkage; improved; member; men; novel; programs; therapy development; tool

DESCRIPTION (provided by applicant): Coronary artery disease is the single leading cause of death in the US. Coronary Artery disease (CAD) is also a leading cause of disability. Identification of genes increasing susceptibility to CAD would have far reaching public health impact from enhancing motivation to make behavioral and lifestyle changes in susceptible individuals to providing basic biological and clinical information about the development and treatment of CAD. CAD is a complex disease with clear genetic and environmental risk factors. Early onset (premature) coronary artery disease (EOCAD), defined as age of onset less than 50 years of age, is known to have a particularly strong genetic component. However the actual genes leading to this increased risk and to a basic understanding of CAD remain obscure. Our goal is to identify genes increasing susceptibility to early onset coronary disease in a large sample of nuclear families with at least two members with EOCAD defined on the basis of a myocardial infarction, surgical procedure, or functional test before the age of 50 in men or 55 in women. We have completed a genome screen for EOCAD using 395 microsatellite markers in 438 families collected by the GENECARD study, a collaborative study involving 6 clinical investigative sites, GlaxoSmithKline and the Duke Center for Human Genetics. We have identified 9 regions providing consistent evidence for linkage in these families. We will concentrate on a region encompassing chromosome 3q13-q22 providing strong and consistent evidence for linkage (MLS=2.3). We propose to perform follow-up genotyping of microsatellite markers in these regions in the original set of families and in an additional set of almost 400 families. Candidate genes in those regions as well as genes identified from expression analyses carried out in other projects will be analyzed using linkage and family-based association. Our efforts in identifying new markers, SNPs and candidate genes for the follow-up studies will be aided by bioinformatics analyses and tools. We strongly believe that a detailed study of genetic factors and gene-environment interactions is an essential step to identifying targeted preventive strategies and more effective treatments.

描述（由申请人提供）：冠状动脉疾病是美国唯一的主要死亡原因。冠状动脉疾病（CAD）也是导致残疾的主要原因。识别增加CAD易感性的基因将对公共卫生产生深远的影响，从增强易感个体改变行为和生活方式的动机到提供有关CAD发展和治疗的基本生物学和临床信息。CAD是一种复杂的疾病，具有明确的遗传和环境风险因素。早发性冠状动脉疾病（EOCAD），定义为发病年龄小于50岁，已知具有特别强的遗传成分。然而，导致这种风险增加的实际基因和对CAD的基本理解仍然不清楚。我们的目标是在一个大样本的核心家族中鉴定增加早发性冠心病易感性的基因，该核心家族中至少有两名成员患有EOCAD，这些EOCAD是基于50岁之前的男性或55岁之前的女性的心肌梗死、外科手术或功能测试定义的。我们使用GENECARD研究收集的438个家族中的395个微卫星标记完成了EOCAD的基因组筛查，该研究是一项涉及6个临床研究中心、葛兰素史克和杜克人类遗传学中心的合作研究。我们已经确定了9个区域，为这些家庭的联系提供了一致的证据。我们将集中在一个区域，包括染色体3q 13-q22提供强有力的和一致的证据连锁（MLS=2.3）。我们建议进行后续的基因分型的微卫星标记在这些地区的原始家庭和一组额外的近400个家庭。这些区域中的候选基因以及从其他项目中进行的表达分析中鉴定的基因将使用连锁和基于家族的关联进行分析。我们将借助生物信息学分析和工具，为后续研究鉴定新的标记、SNP和候选基因。我们坚信，对遗传因素和基因-环境相互作用的详细研究是确定有针对性的预防策略和更有效的治疗方法的重要步骤。

项目成果

Searching for epistatic interactions in nuclear families using conditional linkage analysis.

• DOI: 10.1186/1471-2156-6-s1-s148
• 发表时间: 2005-12-30
• 期刊: BMC GENETICS
• 影响因子: 2.9
• 作者: Shah, SH;Schmidt, MA;Mei, H;Scott, WK;Hauser, ER;Schmidt, S
• 通讯作者: Schmidt, S

High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.

• DOI: 10.1038/msb.2009.11
• 发表时间: 2009
• 期刊: MOLECULAR SYSTEMS BIOLOGY
• 影响因子: 9.9
• 作者: Shah, Svati H.;Hauser, Elizabeth R.;Bain, James R.;Muehlbauer, Michael J.;Haynes, Carol;Stevens, Robert D.;Wenner, Brett R.;Dowdy, Z. Elaine;Granger, Christopher B.;Ginsburg, Geoffrey S.;Newgard, Christopher B.;Kraus, William E.
• 通讯作者: Kraus, William E.

Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis.

• DOI: 10.1007/s00439-008-0619-0
• 发表时间: 2009-03
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Crosslin DR;Shah SH;Nelson SC;Haynes CS;Connelly JJ;Gadson S;Goldschmidt-Clermont PJ;Vance JM;Rose J;Granger CB;Seo D;Gregory SG;Kraus WE;Hauser ER
• 通讯作者: Hauser ER